CLL-Irl Study. ICORG 07-01, V7

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00812669
First received: December 19, 2008
Last updated: January 23, 2014
Last verified: January 2014

December 19, 2008
January 23, 2014
August 2008
June 2021   (final data collection date for primary outcome measure)
Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis [ Time Frame: A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy. ] [ Designated as safety issue: No ]
Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00812669 on ClinicalTrials.gov Archive Site
  • Time to treatment failure (TFF) [ Time Frame: A clinical assessment of response will be made after 4 courses of therapy, Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: at 10 years ] [ Designated as safety issue: No ]
  • Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS [ Time Frame: See description ] [ Designated as safety issue: No ]

    Timing and type of response assessment

    During chemotherapy. A clinical assessment of response will be made after 4 courses of therapy. Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment. A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.

    Following chemotherapy. Disease assessment after the end of therapy will involve a history(recording B-symptoms), complete physical examination, full blood count and blood MRD analysis every 6 months for 5 years and then annually for 5 years or until disease progression.

  • Acute and chronic toxicity as assessed by NCI criteria [ Time Frame: A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy. ] [ Designated as safety issue: Yes ]
  • Time to treatment failure (TFF) [ Designated as safety issue: No ]
  • Overall survival at 10 years [ Designated as safety issue: No ]
  • Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS [ Designated as safety issue: No ]
  • Acute and chronic toxicity as assessed by NCI criteria [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
CLL-Irl Study. ICORG 07-01, V7
An Open-label Phase II Study of the Efficacy and Safety of the Combination of Fludarabine, Cyclophosphamide and Rituximab in Patients With Chronic Lymphocytic Leukaemia Who Are Newly Diagnosed, Have Relapsed or Are Resistant to First-Line Treatment

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fludarabine together with cyclophosphamide and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works in treating patients with chronic lymphocytic leukemia.

OBJECTIVES:

Primary

  • Evaluate the efficacy, in terms of complete remission rate, of fludarabine phosphate, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia.

Secondary

  • Determine the time to treatment failure (TTF) in these patients.
  • Determine the overall survival of these patients at 10 years.
  • Assess the predictive value of immunophenotype, hypermutation analysis, and FISH in determining TTF and OS in these patients.
  • Determine the safety profile of this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes or orally and cyclophosphamide IV or orally on days 1-3 and pegfilgrastim subcutaneously on day 4. Starting on course 2, patients receive rituximab IV on day 1. Treatment repeats every 28 days for up to 6* courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients achieving negative minimal residual disease receive 4 courses of treatment.

Blood samples are collected periodically for biomarker analysis. Samples are analyzed for protein expression (i.e., CD38, CD20, and ZAP70) by flow cytometry; quantitative immunoglobulins, β2-microglobulin, and T-cell subsets by electrophoresis; IgVH mutation status; and cytogenetics (i.e., +12, del 13q, del 11q, and del 17p) by FISH.

After completion of study therapy, patients are followed every 6 months for 5 years and then annually for 5 years.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Biological: pegfilgrastim
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Genetic: cytogenetic analysis
  • Genetic: fluorescence in situ hybridization
  • Genetic: gene expression analysis
  • Genetic: mutation analysis
  • Genetic: protein expression analysis
  • Other: flow cytometry
  • Other: laboratory biomarker analysis
Experimental: Fludarabine, Cylophosphamide and Rituximab
Interventions:
  • Biological: pegfilgrastim
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Genetic: cytogenetic analysis
  • Genetic: fluorescence in situ hybridization
  • Genetic: gene expression analysis
  • Genetic: mutation analysis
  • Genetic: protein expression analysis
  • Other: flow cytometry
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
145
Not Provided
June 2021   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic lymphocytic leukemia

    • Stage I-IV disease (Binet stage progressive A, B, C)
    • CD5 and CD23 positive
    • Untreated OR relapsed/resistant disease after combination chemotherapy or rituximab
    • No 17p deletion

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy > 1 year
  • Creatinine clearance ≥ 50 mL/min
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent malignancy except for noninvasive cervical cancer or localized nonmelanomatous skin cancer
  • No history of anaphylaxis to mouse-derived humanized monoclonal antibody
  • No other severe concurrent (e.g., cardiac or pulmonary) diseases or mental disorders that could interfere with ability to participate in the study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
Both
up to 64 Years
No
Contact information is only displayed when the study is recruiting subjects
Ireland,   United Kingdom
 
NCT00812669
CDR0000629790, ICORG-07-01, 2008-001250-40, EU-20898
Not Provided
ICORG- All Ireland Cooperative Oncology Research Group
ICORG- All Ireland Cooperative Oncology Research Group
Not Provided
Principal Investigator: Elisabeth Vandenberghe, MD St. James's Hospital, Ireland
ICORG- All Ireland Cooperative Oncology Research Group
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP